Many of peptides (proteins) present in the living body have oligosacchrides. The term the “oligosaccharide” refers to a compound comprising monosaccharides which are linked to one another by a glycosyl bond in the form of a chain as shown in FIG. 1.
Oligosaccharides linked to a peptide (protein) are generally divided into two types according to the mode of linkage thereof to amino acids. These two types are asparagine-linked type (N-linked type) comprising an olgisaccharide linked to the side chain of asparagine (Asn), and the mucin-type (O-linked type) comprising an oligosaccharide linked to the side-chain hydroxyl group of serine (Ser) or threonine (Thr). All the asparagine-linked oligosaccharides have a basic skeleton comprising five sugar residues and are divided into the subgroups of the high mannose type, complex type and hybrid type according to the kind of the sugar residue at the non-reducing terminal of the oligosaccharide linked as shown in FIG. 2.
Such oligosaccharides are attached to a peptide (protein), covering the surface of the molecule thereof to thereby adjust the solubility of the peptide (protein), impart resistance to protease and retard metabolism in the blood, further acting to maintain the three-dimensional structure of the peptide (protein).
Typical of the above is a glycopeptide (glycoprotein) which is human erythropoietin (EPO). This glycopeptide (glycoprotein) has a complex-type asparagine-linked oligosaccharide, and is an erythroid differentiation hormone acting on erythroid precursor cells to promote the proliferation and differentiation thereof and thus having the function of maintaining the number of erythrocytes in peripheral blood.
Extensive research has been made on the correlation between the oligosaccharide structure on peptides (proteins) and physiological activity to find that EPO having no oligosaccharide bonded thereto exhibits physiological activity in vitro but fails to exhibit physiological activity in vivo.
Although research has been made not only on such glycopeptides (glycoproteins) but also on various peptides (proteins) for use as pharmaceuticals, a problem still remains to be solved in that peptide (protein) preparations are readily decomposed and metabolized in blood with a protease (peptidase), consequently failing to maintain a sufficient concentration in blood.
An object of the present invention is to provide an aminated complex-type oligosaccharide derivative which can be maintained at a sufficient concentration in blood and a glycopeptide.